Broad objectives of the proposed research are two-fold: first, aqueous humor (AH) dynamics and the treatment of glaucoma; second, pathophysiology of the lens. 1. Transport of major ions and formation of fluid will be studied in posterior chamber of monkey. Attention will be given to the carbonic anhydrase (CA) mediated formation of HCO3-, which appears linked to transport of Na ion and secretion of AH. Transport of Cl- will be studied, with particular attention to new drugs that inhibit Cl reabsorption in kidney but have not been tried in eye. A working hypothesis is that synergism or addition between these two systems will greatly improve means of lowering AH secretion. Since there is some evidence on this from work in cerebrospinal fluid (CSF), and the underlying biochemistry and physiology of AH and CSF are alike, further work in CSF physiology is planned, parallel to that in AH. This can have direct application in medical treatment of hydrocephalus; this goal is important because surgical intervention is far from successful. The pharmacology of two new drug types will be explored in AH and CSF secretion with respect to general suitability for therapy: the furosemide type, and the "irreversible" CA inhibitors. Ongoing work on treatment of glaucoma with a less toxic schedule of methazolamide will be pursued. 2. The role of CA in lens is unknown, in contrast to virtually all other organs. We shall study cation movement and CO2 metabolism in lens under proven conditions of CA inhibition. The reported relation between this enzyme and the appearance of cataracts in man will be analyzed. Experiments in animals will explore whether cataract development is related to loss of CA. Comparative studies will be done between fish (naturally lacking lens CA) and mammals. The program involves a continuum between basic science and clinical medicine.